The Small Intestinal Phase of the Integrated Response to a Meal which the transporter of interest may normally be expressed (e.g., cystinuria). In general, amino acid transporters have reasonably broad specificity and usually transport a subset of amino acids (e.g., neutral, anionic, or cationic) but with some overlap in their affinity for particular amino acids. Furthermore, some (but not all) of the amino acid transporters are symporters that carry their substrate amino acids in conjunction with obligatory uptake of Na+ .
The small intestine is also notable for its ability to take up short peptides (see
Fig. 30.14 ). The primary transporter responsible for such uptake is called peptide transporter 1 (PepT1) and is a symporter that transports peptides in conjunction with protons. Amino acids liberated from these peptides that are not required by the enterocyte are in turn exported across the basolateral membrane and enter blood capillaries to be transported to the liver via the portal vein. PepT1 is also of clinical interest because it can mediate the uptake of so-called peptidomimetic drugs, which include a variety of antibiotics as well as cancer chemotherapeutic agents. The mechanisms by which amino acids and peptidomimetic drugs exit the enterocyte are not fully understood but are presumed to involve additional transport proteins.
Theredundancyinuptakemechanismsfortheproductsofproteindigestionunderscorestheimportanceofthisprocessandalsomeansthatdeficienciesinspecificaminoacidassimilationacrosstheintestinearerelativelyrare.However,undercertaincircumstances,mutationsinproteinsresponsibleforspecificaminoacidtransportcanleadtopathologyinotherorgans.Oneexampleisthediseaseofcysteinuria,whichisamolecularlyheterogeneousdiseaseinvolvingmutationsinavarietyofaminoacidtransporterscapableoftransportingcysteine.Becausecysteinecanalsobeassimilatedacrossthegutintheformofpeptides,nutritionaldeficienciesdonotoccurdespitealackofintestinaluptakemechanismsforthisparticularaminoacid.Incontrast,cysteinecanonlybepoorlyreabsorbedfromtheurineofpatientssufferingfromcystinuria,andkidneystonescanformbecausethisaminoacidisrelativelyinsoluble.PathophysiologycanalsoarisesecondarytomutationsinSLC6A19, aNa+-independenttransporterofneutralaminoacids,andresultinaconditionknownasHartnup disease, arelativelyrareinbornerrorofmetabolismthatcauseslossofneutralaminoacidsinurine,resultinginpsychiatricissues,intellectualdisability,shortstature,headaches,andunsteadygait,althoughnotnutritionaldeficienciesperse.
Lipids, defined as substances that are more soluble in organic solvents than in water, are the third major class of macronutrients making up the human diet. Lipids supply more significant calories on a per-gram basis than proteins or carbohydrates do and are thus of major nutritional significance; they also have a propensity to contribute to obesity if consumed in excessive amounts. Lipids also dissolve volatile compounds that contribute to food’s taste and aroma.